Lecturer: Shirene M.

Singh
VETM 3004-LECTURE#2 Date: Friday 6th September,
2019
CELLS OF THE IMMUNE SYSTEM Time: 8-9 am
OBJECTIVES
Describe the structure and function of the macrophage, monocyte, neutrophil,
dendritic cell and mast cell.
Describe the process by which nitric oxide is generated by macrophages.
Explain the role of the macrophage in granuloma formations.
Explain the role of macrophages in the removal of foreign material from the
bloodstream.
Describe the morphological features of the eosinophil and basophil.
Describe the structure and list the functions of the natural killer (NK) cell.
CELLS IN WHOLE BLOOD

If we were to
collect whole
blood from an
animal using a
lavender cap
tube/purple top
tube, which
types of cells
can we expect
to find?
TYPICAL TYPES OF WHITE BLOOD CELLS IN A WBC
PROFILE
These cells exist within
particular ranges in normal
animals

An abnormality in these
ranges is associated with
inflammatory responses,
infection or a diseased state

What are the terms given to increases

or decreases in the levels of these
cells?
BUFFY COAT AND PLASMA

Centrifugation

Buffy coat- a layer of white blood cells found between

the plasma and packed RBCs following centrifugation of
whole blood
DIFFERENTIATION OF CELLS OF THE IMMUNE
SYSTEM
NB: Recent discoveries
have revealed that
natural killer cells can be
derived from either
lymphoid or myeloid
lineages.

Adapted from: oerpub.github.io/epubjs-demo-book/content

GRANULOCYTES Polymorphonuclear
Phagocytosis, leukocytes (shape of nuclei)
inflammation,
antimicrobial Possess densely staining
functions cytoplasmic granules

Parasitic
Short-lived-survive for a few
days
immunity, allergic
responses ↑ #s during immune
response-migrate from
Allergic blood to sites of infection or
responses and inflammation
inflammation
GRANULOCYTES-MAST CELLS
Derived from the myeloid stem cell Granules contain histamine, heparin,
leukotrienes, kallikreines, chymase,
Role in allergic inflammation, tryptase etc.
anaphylaxis, wound healing, innate
immunity etc.
Located close to the body surface
where inflammatory mediators are
released
Large, round cells located in
connective tissues, under mucosal
surfaces, around nerves, under skin, Adapted from: marvistavet.com/sites

in intestines and airways

MAST CELLS
Stimuli that cause degranulation of mast cells:
IgG and antigen
IgE and antigen
Neuropeptides
Adenosine
Endothelins
Lipopolysaccharides
NEUTROPHILS
 10-20 µm in diameter
 Dense chromatin in nucleus, small golgi apparatus, few ribosomes, some
mitochondria and some rough ER
 Do not take up basic or acidic dyes
 Short-lived (few days), undergo apoptosis and are removed by macrophages
 Remain in the blood (around 12 hours) after production in bone marrow prior
to migration to tissues
 Can have as much as a 10-fold increase in number in bacterial infections
 Granules can be primary, secondary or tertiary
NEUTROPHILS

Adapted from : neoreviews.aappublications.org/content/8/9

ANTIMICROBIAL FUNCTIONS OF NEUTROPHILS
Degranulation→ 3 types of granules
 Primary (azurophilic)-myeloperoxidase, defensins, lysozyme, serine
proteases, elastase, cathepsin G etc.
 Secondary-alkaline phosphatase, cathelicidins, NADPH oxidase, lysozyme,
collagenase, lactoferrin etc.
 Tertiary-cathepsin, collagenase, gelatinase etc.

Neutrophil extracellular traps (NETs):

a mechanism for killing extracellular bacteria consisting of the release
of web-like structures of DNA made of chromatin and serine proteases into
extracellular fluid
ANTIMICROBIAL FUNCTIONS OF NEUTROPHILS
Phagocytosis
 recognize pathogens coated with opsonins
 engulfed pathogens enter intracellular vesicles where they
are exposed to degradative enzymes and antimicrobial
molecules

“Respiratory burst”
STAGES IN THE PROCESS OF PHAGOCYTOSIS
Chemotaxis
Movement along a chemotactic gradient toward sites of microbial invasion
Examples of chemoattractants: C5a, fibrinopeptide B and hydrogen
peroxide
Adherence
Requires overcoming a zeta-potential; opsonins mannose-binding lectin,
fibronectin, some complement components and antibodies
Ingestion-Involves the action of lamellipods
Destruction
Respiratory burst-generation of superoxide anion, H2O2, singlet oxygen,
hypochlorite etc. (ROS)
Lytic enzymes and antimicrobial peptides found in intracellular granules
(phagolysosome formation)
NEUTROPHIL PHAGOCYTIC RECEPTORS

Figure 2-32-The immune system, 3rd ed

MONOCYTES
 Derived from the common myeloid progenitor, round cells, 15 to 20 µm
 Found in the blood, bone marrow and spleen
 Migrate from the blood to the tissues during infection
 Role in phagocytosis
 Possess chemokine and pattern recognition receptors on their surfaces
 During inflammation, they can differentiate into inflammatory dendritic cells
(DCs) or macrophages
 Replenish the population of tissue macrophages
MACROPHAGES
Phagocytic cells that kill invading microbes, derived from multiple sources
Produce cytokines that have a role in innate and adaptive immune responses
Role in inflammation
Promote the recruitment of neutrophils, e.g. TNF-α
Remove dead, dying and damaged cells, important in healing
Reside in different tissues and are named accordingly
Classified as M1 (inflammation) or M2 cells (suppress inflammation and
promote tissue repair)
MACROPHAGES MONONUCLEAR PHAGOCYTIC SYSTEM

Source: veteriankey.com/wp-content/uploads
MACROPHAGE STRUCTURE

Source: britannica.com/science/macrophage
PHAGOCYTIC RECEPTORS
A B

A-Figure 1-10-immunobiology, 7th ed

B-Figure 2-32-The immune system, 3rd ed
PROFESSIONAL PHAGOCYTIC CELLS

studyblue.com/notes/note/n/hematology/deck/12464831

Image:
3c1703fe8d.site.internapcdn.net/newman/gfx/
news/2016/ljiscientist.jpg

Image: quora.com/How-were-dendritic-cells-
discovered
PROFESSIONAL (INNATE) ANTIGEN PRESENTING CELLS

Image: cellular-immunity.blogspot.com/2007/12/
Image: quora.com/How-were-dendritic-cells-discovered
macrophages.html
 IMPORTANT MACROPHAGE CYTOKINES AND THEIR
FUNCTIONS

Adapted from: veteriankey.com/innate-immunity-macrophages-and-recovery-from-inflammation/

NITRIC OXIDE PRODUCTION
Species differences in the generation of
reactive nitrogen species (RNS)
PAMPS (pattern-associated molecular
patterns) result in macrophage
expression of type 2 nitric oxide
synthase (NOS2)
Cattle, sheep, horses and laboratory
rodents
NOS2 converts L-arginine and oxygen to
citrulline and nitric oxide (NO)
NO+ superoxide anion RNS

Adapted from: veteriankey.com/innate-immunity-macrophages-and-recovery-from-inflammation/

GRANULOMA FORMATION

ADAPTED FROM: MINI REVIEW ARTICLE

Front. Immunol., 22 April 2013, Guirado Evelyn, Schlesinger Larry
DENDRITIC CELLS
 There are two major categories of DCs, both of which originate from the
hematopoietic stem cells in the bone marrow
 Conventional DCs (cDCs), plasmacytoid DCs (pDCs)
 pDCs produce high levels of type 1 interferon (INF-1) and are important in
antiviral immune responses
 cDCs can be found in the thymus, spleen and lymph nodes
 Blood-derived (CD4 and CD8) or resident DCs (CD4+, CD8+ or CD4-8-)
 Migratory DCs-found in local draining lymph nodes, largely absent from
spleen and thymus; they traffic from peripheral tissues to lymph nodes
NATURAL KILLER CELLS
Derived from either the lymphoid or myeloid progenitor
Found in the blood and secondary lymphoid organs
Important role in the early response to virus infection (prior to
CD8+ cytotoxic T cell activation) and tumour cell recognition
Antibody-dependent cell-mediated cytotoxicity (tumour cells)

Adapted from: naturale-cell.com/nk-cells

NATURAL KILLER CELLS
Killing is related to the release of cytotoxic granules containing
granzymes and perforin→ programmed cell death
Killing is triggered by germline-encoded receptors→ target cells and
is enhanced by cytokines such as IL-12 with IL-18 and type 1
interferons

Image: Prospects for the use of NK cells

in immunotherapy of human cancer.
Hans-Gustaf Ljunggren and Karl-Johan Malmberg.
Nature Reviews Immunology. June 2007.
SUMMARY
Professional phagocytic cells include neutrophils, macrophages and dendritic
cells
Neutrophils are recruited to sites of infection during early stages of the
immune response
Macrophages are slower to respond but are capable of sustained
phagocytic activity
Phagocytic cells possess a number of surface receptors to allow them to carry
out their function
Granulocytes include neutrophils, eosinophils and basophils
Eosinophils and basophils are implicated in allergic reactions
SUMMARY
Monocytes are capable of differentiating into macrophages or dendritic cells
Granuloma formation is associated with chronic inflammation with mononuclear
cell infiltration and fibrosis
Dendritic cells are conventional or plasmacytoid
Mast cells undergo degranulation after exposure to several different stimuli
Natural killer cells are important for antiviral immune responses and
recognition of tumours